title: Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia.
abstract: This study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sysmex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 × 10⁹/L, P < .01), whereas IPF percentage was greater (29.2% vs 3.2%, P < .01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-FcγRIII antibody, had corresponding A-IPF responses. Seven of 7 patients responding to RhoD immuneglobulin (anti-D) and 6 of 8 responding to intravenous immunoglobulin (IVIG) did not have corresponding increases in A-IPF, but 2 with IVIG and 1 with IVIG anti-D did. This supports inhibition of platelet destruction as the primary mechanism of intravenous anti-D and IVIG, although IVIG may also enhance thrombopoiesis. Plasma glycocalicin, released during platelet destruction, normalized as glycocalicin index, was higher in ITP patients than controls (31.36 vs 1.75, P = .001). There was an inverse correlation between glycocalicin index and A-IPF in ITP patients (r² = -0.578, P = .015), demonstrating the relationship between platelet production and destruction. Nonresponders to thrombopoietic agents had increased megakaryocytes but not increased A-IPF, suggesting that antibodies blocked platelet release. In conclusion, A-IPF measures real-time thrombopoiesis, providing insight into mechanisms of treatment effect.
authors.affiliation: Platelet Disorders Center, Department of Pediatrics, Weill-Cornell Medical College, New York, NY, USA. sarahbarsam@gmail.com
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Barsam
authors.forename: Bethan
authors.initials: B
authors.lastname: Psaila
authors.forename: Marc
authors.initials: M
authors.lastname: Forestier
authors.forename: Lemke K
authors.initials: LK
authors.lastname: Page
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sloane
authors.forename: Julia T
authors.initials: JT
authors.lastname: Geyer
authors.forename: Glynis O
authors.initials: GO
authors.lastname: Villarica
authors.forename: Mary M
authors.initials: MM
authors.lastname: Ruisi
authors.forename: Terry B
authors.initials: TB
authors.lastname: Gernsheimer
authors.forename: Juerg H
authors.initials: JH
authors.lastname: Beer
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007223:Infant; D007518:Isoantibodies / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D011720:Pyrazoles / Q000627:therapeutic use; D017452:Receptors, IgG / Q000276:immunology; D012189:Retrospective Studies; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; D013922:Thrombocytosis; D034061:Thrombopoiesis / Q000187:drug effects*; D055815:Young Adult
chemical_list: D001565:Benzoates; D006834:Hydrazines; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D011720:Pyrazoles; C061961:RHO(D) antibody; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C520809:eltrombopag